Cesium carbonate → HCID 87055064, compound

HRID 2201586Notes

Reaction equation

HRID 2201586 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:9]2=[O:12])=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:40]=[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])[C:38](B4OC(C)(C)C(C)(C)O4)=[CH:37][C:31]=3[C:32]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[F:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([C:38]4[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:40][C:30]5[O:29][C:28]([C:25]6[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=6)=[C:32]([C:33]([NH:35][CH3:36])=[O:34])[C:31]=5[CH:37]=4)=[CH:3][CH:4]=3)[C:9]2=[O:12])=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 117771288HCID 117771288, compound

Product 1

HCID 87055064HCID 87055064, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 7-bromo-2-(4-fluorobenzyl)-3,4-dihydroisoquinolin-1(2H)-one (222 mg, 0.66 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (200 mg, 0.40 mmol) in 1,4-dioxane (5 mL) and water (200 μl) was added Cs2CO3 (260 mg, 0.80 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (26 mg, 0.04 mmol) under N2 protection. The resulting mixture was heated to 90° C. and stirred at this temperature for 3 h. The reaction was cooled, filtered through a pad of celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. The resulting residue was purified using column chromatography (eluted with 0-30% EtOAc/DCM) to provide 5-(2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (240 mg, yield: 96%). MS (M+H)+: 630.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of celite
  3. washwashed with ethyl acetate
  4. customThe combined filtrate was evaporated in vacuo
  5. customThe resulting residue was purified
  6. washcolumn chromatography (eluted with 0-30% EtOAc/DCM)

Sources & evidence

ORD record
ord-6b24603726fc4d19827162d4c28bc974
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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